RESUMO
BACKGROUND: Ligand-independent activation of the androgen receptor (AR) by cytokines has been implicated in the progression of androgen-independent prostate cancer (PCa). To determine the potential effects of elevated levels of interleukin-4 (IL-4) in patients with PCa, six different cytokines were examined for their ability to activate the AR. MATERIALS AND METHODS: LNCaP cells were transiently transfected with prostate-specific antigen (PSA) (-630 / +12)-luciferase and treated with R1881, six kinds of cytokines including IL-4, or vehicle. Transactivation assays were also performed in LNCaP cells co-transfected with the 5xGal4UAS-TATA-luciferase and AR-(1-558)-Gal4DBD prior to incubation with R1881, IL-4, IL-6, or vehicle. Seventy-two patients with pre-treatment PCa, 17 patients with hormone-refractory metastatic PCa receiving androgen ablation therapy, 20 patients with benign prostatic hypertrophy and 10 healthy male volunteers were enrolled in this retrospective study. The concentration of serum IL-4 was measured by chemiluminescence enzyme immunoassay. RESULTS: IL-4 induced androgen-response element-driven reporters and activated the AR N-terminal domain (NTD) in a ligand-independent manner in transiently transfected LNCaP cells. Levels of IL-4 in the serum were significantly elevated in patients with hormone-refractory PCa as compared to the levels in pre-treatment PCa. CONCLUSION: IL-4 serum levels were demonstrated to be increased in honnone-refractory PCa and IL-4 was shown to enhance PSA reporter gene activity by the activation of AR NTD in human LNCaP cells. These results suggest that the AR can be activated by cytokines, and that this mechanism may play an important role in the transition from androgen-dependent to androgen-independent PCa after patients receive androgen ablation therapy.
Assuntos
Interleucina-4/sangue , Neoplasias da Próstata/sangue , Adulto , Idoso , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-4/farmacologia , Masculino , Metribolona/farmacologia , Neoplasias Hormônio-Dependentes/sangue , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Regiões Promotoras Genéticas , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , TransfecçãoRESUMO
<p><b>AIM</b>To evaluate the occurrence and prevalence of microdeletions in the gamma chromosome of patients with azoospermia.</p><p><b>METHODS</b>DNA from 29 men with idiopathic azoospermia was screened by polymerase chain reaction (PCR) analysis with a set of gamma chromosome specific sequence-tagged sites (STSs) to determine microdeletions in the gamma chromosome.</p><p><b>RESULTS</b>Deletions in the DAZ (deleted in azoospermia) loci sgamma254 and sgamma255 were found in three patients with idiopathic azoospermia, resulting in an estimated frequency of deletions of 10.7% in idiopathic azoospermia men.</p><p><b>CONCLUSION</b>We conclude that PCR analysis is useful for the diagnosis of microdeletions in the Y chromosome, which is important when deciding the suitability of a patient for assisted reproductive technology such as testicular sperm extracion-intracytoplasmic sperm injection (TESE-ICSI).</p>
Assuntos
Adulto , Humanos , Masculino , Sequência de Bases , Cromossomos Humanos Y , Primers do DNA , Eucromatina , Genética , Hormônio Foliculoestimulante , Sangue , Heterocromatina , Genética , Hormônio Luteinizante , Sangue , Oligospermia , Sangue , Genética , Reação em Cadeia da Polimerase , Prolactina , Sangue , Deleção de Sequência , Genética , Sitios de Sequências Rotuladas , Testosterona , SangueRESUMO
<p><b>AIM</b>Chromosome 13 is one of the most frequently altered chromosomes in prostate cancer. The present study was undertaken to examine the role of human chromosome 13 in the progression of prostate cancer.</p><p><b>METHODS</b>Human chromosome 13 was introduced into highly metastatic rat prostate cancer cells via microcell-mediated chromosome transfer.</p><p><b>RESULTS</b>Microcell hybrid clones containing human chromosome 13 showed suppression of metastasis to the lung without any suppression of tumorigenicity, except for one clone, which contained the smallest sized human chromosome 13 and did not show any suppression on lung metastasis. Expression of two known tumor suppressor genes, BRCA2 and RB1, which map to chromosome 13, was examined by reverse transcription- polymerase chain reaction analysis. BRCA2 was expressed only in the metastasis-suppressed microcell-hybrid clones, whereas RB1 was expressed in all clones.</p><p><b>CONCLUSION</b>Human chromosome 13 contains metastasis suppressor gene(s) for prostate cancer derived from rat. Furthermore, the RB1 gene is unlikely to be involved in the suppression of metastasis evident in this system.</p>
